Human Gene Module / Chromosome 10 / ZMIZ1

ZMIZ1zinc finger MIZ-type containing 1

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
20 / 0
Aliases
ZMIZ1, MIZ,  NEDDFSA,  RAI17,  TRAFIP10,  ZIMP10
Associated Syndromes
-
Chromosome Band
10q22.3
Associated Disorders
ADHD, ASD
Relevance to Autism

Analysis of whole-genome sequencing data in Liu et al., 2018 demonstrated that a distal enhancer putatively targeting the ZMIZ1 gene harbored recurrent de novo single-nucleotide variants in ASD-affected cases. Carapito et al., 2019 reported 19 individuals with ZMIZ1 variants presenting with a neurodevelopmental syndrome characterized by developmental delay/intellectual disability, growth failure, feeding difficulties, microcephaly, facial dysmorphism, and various other congenital malformations; behavioral abnormalities, including autism spectrum disorder, were frequently observed in affected individuals.

Molecular Function

This gene encodes a member of the PIAS (protein inhibitor of activated STAT) family of proteins. The encoded protein regulates the activity of various transcription factors, including the androgen receptor, Smad3/4, and p53. The encoded protein may also play a role in sumoylation.

SFARI Genomic Platforms
Reports related to ZMIZ1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support A de novo t(10;19)(q22.3;q13.33) leads to ZMIZ1/PRR12 reciprocal fusion transcripts in a girl with intellectual disability and neuropsychiatric alterations Crdova-Fletes C , et al. (2015) No Behavioral abnormalities
2 Primary A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies Liu Y , et al. (2018) Yes -
3 Recent recommendation ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder Carapito R , et al. (2019) No ASD
4 Support Autosomal dominant inheritance in a recently described ZMIZ1-related neurodevelopmental disorder: Case report of siblings and an affected parent Latchman K , et al. (2019) No ADHD, autistic features
5 Support - Mahjani B et al. (2021) Yes -
6 Support - Woodbury-Smith M et al. (2022) Yes -
7 Support - Brea-Fernández AJ et al. (2022) No -
Rare Variants   (20)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo NA Simplex 30639322 Carapito R , et al. (2019)
- - translocation De novo NA Simplex 26163108 Crdova-Fletes C , et al. (2015)
c.1744A>G p.Asn582Asp missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.3097-2A>G - splice_site_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.2456C>T p.Thr819Met missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.272A>G p.Lys91Arg missense_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.2835+4A>T - splice_region_variant De novo NA - 35322241 Brea-Fernández AJ et al. (2022)
c.859G>A p.Ala287Thr missense_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.887C>A p.Thr296Lys missense_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.887C>T p.Thr296Ile missense_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.893C>T p.Thr298Ile missense_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.899C>T p.Thr300Met missense_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.2610C>T p.Ser870= synonymous_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.1386dup p.Thr463HisfsTer14 frameshift_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.2758dup p.Gln920ProfsTer34 frameshift_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.2835del p.Met946CysfsTer61 frameshift_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.3021del p.Phe1008LeufsTer7 frameshift_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.3112dup p.Thr1038AsnfsTer4 frameshift_variant De novo NA Simplex 30639322 Carapito R , et al. (2019)
c.1386dup p.Thr463HisfsTer14 frameshift_variant Unknown - Multiplex 30639322 Carapito R , et al. (2019)
c.1310del p.Pro437ArgfsTer84 frameshift_variant Familial Paternal Multiplex 31833199 Latchman K , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2S

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
icon
2S

Increased from to 2S

Krishnan Probability Score

Score 0.52341583538816

Ranking 1650/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.9997437008725

Ranking 812/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.94627625165325

Ranking 16805/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score

Score 0.41481032923338

Ranking 1290/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
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